NEUROTENSIN MODULATION OF ACETYLCHOLINE AND GABA RELEASE FROM THE RATHIPPOCAMPUS - AN IN-VIVO MICRODIALYSIS STUDY

The effects of neurotensin (NT) on the release of acetylcholine (ACh), aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) f rom the hippocampus of freely moving rats were studied by transversal microdialysis. ACh was detected by High Performance Liquid Chromatogra phy (HPLC) with electrochemical detection while GABA, glutamate and as partate were measured using HPLC with fluorometric detection. Neuroten sin (0.2 and 0.5 mu M) administered locally through the microdialysis probe to the hippocampus produced a long-lasting and concentration-dep endent increase in the basal extracellular levels of GABA and ACh but not of glutamate and aspartate. The increase in the extracellular leve ls of GABA and ACh produced by 0.5 mu M neurotensin in the hippocampus reached a maximum of about 310% for GABA and 250% for ACh. This stimu lant effect of NT was antagonized by the NT receptor antagonist SR 486 92 (100 mu g/kg, i.p.). Local infusion of tetrodotoxin (1 mu M) decrea sed the basal release of ACh, GABA, Asp, Glu and prevented the 0.2 mu M NT-induced increase in GABA and ACh release. The effect of NT on the release of ACh was blocked by the GABA, receptor antagonist bicuculli ne (2-10 mu M) Our findings indicate for the first time that neurotens in plays a neuromodulatory role in the regulation of GABAergic and cho linergic neuronal activity in the hippocampus of awake and freely movi ng rats. The potentiating effects of neurotensin on GABA and ACh relea se in the hippocampus are probably mediated by (i) NT receptors locate d on GABAergic cell bodies and (ii) through GABA, receptors located on cholinergic nerve terminals. (C) 1998 Elsevier Science Ltd. All right s reserved.